Exploration of novel isoniazid embedded 1,3,4-oxadiazole hybrids as anti-TB, antioxidant, and COX inhibitors: synthesis, spectral analysis, and molecular modeling studies

Journal of the Iranian Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Язык: Английский

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Functionalized Triazoles: Design, Synthesis and Chemical Characterization of 1,2,3-triazolylmethylthio-1,3,4-oxadiazole derivatives as Insecticidal and Antibacterial Agents

Journal of the Indian Chemical Society, Год журнала: 2025, Номер 102(2), С. 101578 - 101578

Опубликована: Янв. 11, 2025

Язык: Английский

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Unlocking InhA: Novel approaches to inhibit Mycobacterium tuberculosis

Bioorganic Chemistry, Год журнала: 2024, Номер 146, С. 107250 - 107250

Опубликована: Март 5, 2024

Язык: Английский

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Design, synthesis, characterization, and biological evaluation of novel pyrazine-1,3,4-oxadiazole/[1,2,4] triazolo[3,4-b][1,3,4]thiadiazine hybrids as potent antimycobacterial agents

Journal of Molecular Structure, Год журнала: 2024, Номер 1304, С. 137657 - 137657

Опубликована: Янв. 27, 2024

Язык: Английский

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Synthesis, Computational Studies, Antioxidant and Anti-Inflammatory Bio-Evaluation of 2,5-Disubstituted-1,3,4-Oxadiazole Derivatives

Pharmaceuticals, Год журнала: 2023, Номер 16(7), С. 1045 - 1045

Опубликована: Июль 24, 2023

The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flurbiprofen moiety with the aim to explore potential of target molecules decrease oxidative stress. title compounds were prepared simple reactions in which a -COOH group was esterified methanol an acid-catalyzed medium, then reacted hydrazine afford corresponding hydrazide. acid hydrazide cyclized into 1,3,4-oxadiazole-2-thiol reacting CS2 presence KOH. reaction -SH various alkyl/aryl chlorides, involves S-alkylation reaction. structures ascertained spectroscopic data. silico molecular docking performed against proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 6Y3C) determine binding affinity these structures. It has inferred that most bind well active site 5KIR compared 6Y3C, especially compound Ox-6f showed excellent (7.70 kcal/mol) among all Ox-6a-f. dynamic (MD) simulation also check stability complexes ligands determining their root mean square deviation fluctuation. Little fluctuation observed case Ox-6f, forms stable complex COX-2. comprehensive antioxidant evaluated free radical scavenging activity, including DPPH, OH, nitric oxide (NO), iron chelation assay. derivative promising results 80.23% at dose 100 µg/mL while ascorbic exhibited 87.72% inhibition same dose. anti-inflammatory activity final products performed, inflammatory markers assayed, such as thiobarbituric acid-reducing substance, oxide, interleukin-6 (IL-6), Ox-6d displayed higher exhibiting 70.56% 74.16% respectively. standard ibuprofen, 84.31% dose, 200 µg/mL. following carrageen-induced hind paw edema model, 79.83% reduction volume reduced volume. As dry lab wet confirm each other, it deduced may serve lead structure design potent address

Язык: Английский

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BTEAC Catalyzed Ultrasonic-Assisted Synthesis of Bromobenzofuran-Oxadiazoles: Unravelling Anti-HepG-2 Cancer Therapeutic Potential through In Vitro and In Silico Studies

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 3008 - 3008

Опубликована: Фев. 3, 2023

In this work, BTEAC (benzyl triethylammonium chloride) was employed as a phase transfer catalyst in an improved synthesis (up to 88% yield) of S-alkylated bromobenzofuran-oxadiazole scaffolds BF1-9. These structural hybrids BF1-9 were evaluated vitro against anti-hepatocellular cancer (HepG2) cell line well for their silico therapeutic potential six key targets, such EGFR, PI3K, mTOR, GSK-3β, AKT, and Tubulin polymerization enzymes. Bromobenzofuran motifs BF-2, BF-5, BF-6 displayed the best anti-cancer with least viabilities (12.72 ± 2.23%, 10.41 0.66%, 13.08 1.08%), respectively, HepG2 liver line, they also showed excellent molecular docking scores enzymes, which are major targets. Bromobenzofuran-oxadiazoles binding affinities active sites enzymes studies MMGBSA MM-PBSA studies. The stable bindings these enzyme targets EGFR PI3K further confirmed by dynamic simulations. investigations revealed that 2,5-dimethoxy-based BF-5 (10.41 0.66% viability) exhibited cytotoxic efficacy. Moreover, computational suggested probable scaffold. approaches, docking, dynamics simulations, DFT studies, association experimental biological data bromobenzofuran-oxadiazoles Thus, results anticipate synthesized hybrid possesses prominent anti-liver inhibitory effects can be used lead investigation anti-HepG2 therapy.

Язык: Английский

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Synthesis of trifluoromethylpyrrolopyrazole derivatives via [3+2] cycloaddition of trifluoromethyl N-acylhydrazones or trifluoroacetohydrazonoyl bromides with maleimides

Tetrahedron, Год журнала: 2023, Номер 136, С. 133353 - 133353

Опубликована: Март 15, 2023

Язык: Английский

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Synthetic Transformation of 4-fluorobenzoic Acid to 4-fluorobenzohydrazide Schiff Bases and 1,3,4-Oxadiazole Analogs having DPPH Radical Scavenging Potential

Letters in Drug Design & Discovery, Год журнала: 2022, Номер 20(12), С. 2018 - 2024

Опубликована: Ноя. 2, 2022

Aims: Synthesis of 4-fluorobenzohydrazide Schiff bases and 1,3,4-oxadiazole analogs has a DPPH radical scavenging potential. Background: Synthetic antioxidants are widely used because they effective cheaper than natural antioxidants. Based on the literature survey, this present study is mainly focused free activity base oxadiazole motifs. Methods: In research work, Schiff’s (4a-4g) (5a-5g) derivatives based 4-fluorobenzoic acid were synthesized through multistep reactions. Initially, was esterified in presence sulphuric (H2SO4) ethanol solvent, then it reacted with an excess hydrazine hydrate to obtain desired 4-fluorobenzohydrazide. Various aromatic aldehydes 4-fluorobenzo hydrazide catalytic amount acetic hydrazones. Finally, different substituted hydrazones cyclized iodine potassium carbonate DMSO 1,3,4-oxadiazoles. The progress all reactions checked using thin-layer chromatography. compounds recrystallized from good yield. characterized help EI-MS 1H-NMR spectroscopy. Results: demonstrated activity. Among series, Compound 4f (IC50 = 25.57 ± 7.41 μM), showed comparable when compared standard Vitamin C 19.39 12.57 μM). Similarly 4a 40.90 1.92 4b 34.77 1.03 4c 90.2 2.90 4e 78.62 9.64 4g 80.65 1.80 5a 52.67 4.98 μM) 5f 89.45 9.11 moderate antioxidant Furthermore compounds, 4d 102.55 10.4 5b 123.76 12.34 5d 701.62 1.06 5e 102.87 7.98 displayed less significant anti-oxidant potential, while 5c 5g found inactive. Conclusion: 4- fluorobenzoic scaffolds pathways. All structurally spectroscopy evaluated for their vitro In-vitro reveals that newly prepared have potent Whereas compound inactive, recognized series potential molecules as agents useful field medicinal chemistry.

Язык: Английский

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Novel 5-bromoindole-2-carboxylic Acid Derivatives as EGFR Inhibitors: Synthesis, Docking Study, and Structure Activity Relationship

Anti-Cancer Agents in Medicinal Chemistry, Год журнала: 2023, Номер 23(11), С. 1336 - 1348

Опубликована: Фев. 27, 2023

The indole backbone is encountered in a class of N-heterocyclic compounds with physiological and pharmacological effects such as anti-cancer, anti-diabetic, anti-HIV. These are becoming increasingly popular organic, medicinal, pharmaceutical research. Nitrogen compounds' hydrogen bonding, dipole- dipole interactions, hydrophobic effects, Van der Waals forces, stacking interactions have increased their relevance chemistry due to improved solubility. Indole derivatives, carbothioamide, oxadiazole, triazole, been reported act anti-cancer drugs ability disrupt the mitotic spindle prevent human cancer cell proliferation, expansion, invasion.To synthesize new 5-bromoindole-2-carboxylic acid derivatives that function EGFR tyrosine kinase inhibitors deduced through molecular docking studies.Different (carbothioamide, tetrahydro pyridazine-3,6-dione, triazole) were synthesized evaluated different chemical, spectroscopic methods (IR, 1HNMR, 13CNMR, MS) assessed silico vitro for antiproliferative activities against A549, HepG2, MCF-7 lines.According analyses, 3a, 3b, 3f, 7 exhibited strongest domain binding energies. In comparison erlotinib, which displayed some hepatotoxicity, all ligands good absorption levels, did not appear be cytochrome P450 inhibitors, hepatotoxic. found decrease growth three types lines (HepG2, MCF-7), compound 3a being most powerful while still cancer-specific. Cell cycle arrest activation apoptosis results 3a's inhibition activity.The novel particular, promising agents inhibit proliferation by inhibiting activity.

Язык: Английский

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Investigation of Novel 2‐(Chloromethyl)‐5‐(3, 5‐Disubstituted‐1H‐Indol‐2‐yl)‐1,3,4‐Oxadiazole Derivatives as In Vitro, and In Silico Bioactivity Potential: Anti‐inflammatory, Anti‐TB and Antioxidant Activities Study

ChemistrySelect, Год журнала: 2024, Номер 9(33)

Опубликована: Сен. 4, 2024

Abstract A series of novel 2‐(chloromethyl)‐5‐(3, 5‐disubstituted‐1 H ‐indol‐2‐yl)‐1,3,4‐oxadiazole ( 3 a – h ) derivatives have been synthesized as potential COX inhibitors, anti‐TB, and anti‐oxidant activities. The structures were confirmed by IR, NMR 1 13 C) mass spectral techniques. physicochemical properties, ADME, drug‐likeness profile for the compounds evaluated SwissADME. Based on our interest in indole chemistry SAR study, foresaid examined vitro inhibitory activity, antioxidant ADME studies disclosed newly compounds. , b c recognized outstanding COX‐II inhibitions with IC 50 values 0.28, 0.24, 0.45 μM compared to standard drugs. ,and showed anti‐TB activity MIC value 0.78 μg/mL. attested at 10 μg/ml rate inhibition 66.52 %, 68.25 65.95 % respectively. Finally, molecular docking carried out cyclooxygenase‐2 PDB ID: 6COX ), M. tuberculosis enoyl reductase (INHA) complexed 1‐cyclohexyl‐ N ‐(3,5‐dichlorophenyl)‐5‐oxopyrrolidine‐3‐carboxamide 4TZK cytochrome peroxidase 2X08 all derivatives. selected taken their dynamic studies.

Язык: Английский

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